Cohort study of fatty acid synthase expression and patient survival in colon cancer

Abstract

Purpose: Energy balance seems to be important in the pathogenesis of colon cancer. Fatty acid synthase (FASN) is physiologically regulated by energy balance and is often upregulated in colorectal cancer. Nonetheless, the influence of FASN expression on patient outcome is uncertain.

Patients and methods: Using the database of 647 patients with colon cancer in two independent cohort studies, FASN overexpression was detected in 84 tumors (13%) by immunohistochemistry. Cox proportional hazards models calculated hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylation phenotype.

Results: There were 279 deaths, including 160 colon cancer-specific deaths. FASN overexpression was associated with a significant reduction in colon cancer-specific mortality by both univariate and multivariate analyses (adjusted HR, 0.41; 95% CI, 0.19 to 0.89) and an insignificant trend toward improved overall mortality (adjusted HR, 0.75; 95% CI, 0.50 to 1.13). Notably, the effect of FASN expression on mortality might be different according to body mass index (BMI; P(interaction) = .019); the adjusted HR of overall mortality for FASN overexpression was 0.63 (95% CI, 0.39 to 1.02) among patients with BMI less than 27.5 kg/m(2) and 2.91 (95% CI, 1.19 to 7.12) among those with BMI >or= 27.5 kg/m(2). Moreover, the adverse effect of moderate overweight/obesity on overall survival was limited to FASN-positive tumors (adjusted HR, 4.10; 95% CI, 1.14 to 14.8; BMI >or= 27.5 kg/m(2) v < 27.5 kg/m(2)). CONCLUSION Among nonobese patients with colon cancer, tumoral FASN overexpression is associated with improved survival, whereas among moderately overweight or obese patients (BMI >or= 27.5 kg/m(2)), FASN overexpression may predict a worse outcome.

Fig 1.

Fatty acid synthase (FASN) expression in colon cancer. (A) No FASN expression in colon cancer (arrow). (B) Little FASN expression in colon cancer (negative for FASN overexpression; arrows). (C) Weak FASN expression in colon cancer (negative for FASN overexpression; open arrowhead). (D) Strong FASN expression in colon cancer (positive for FASN overexpression; open arrow).

Fig 2.

Kaplan-Meier curves for (A) colon cancer–specific survival and (B) overall survival according to tumoral fatty acid synthase (FASN) expression.

Fig 3.

Stratified analysis of fatty acid synthase (FASN) and colon cancer–specific mortality. Adjusted hazard ratios (HRs) with 95% CI for FASN-positive tumors (compared with FASN-negative tumors) in various strata are shown. Adjusted HRs are consistently less than 1, indicating lower mortalities associated with FASN-positive tumors. *95% CI is not shown because of no colon cancer–specific deaths among patients with FASN-positive tumors that were microsatellite instability (MSI) high, CpG island methylation phenotype (CIMP) high, or BRAF positive. HPFS, Health Professionals Follow-Up Study; MSS, microsatellite stable; NHS, Nurses’ Health Study.